Unleashing the Potential of Camptothecin: Exploring Innovative Strategies for Structural Modification and Therapeutic Advancements

Journal of Medicinal Chemistry, Год журнала: 2024, Номер 67(5), С. 3244 - 3273

Опубликована: Фев. 29, 2024

Camptothecin (CPT) is a potent anti-cancer agent targeting topoisomerase I (TOP1). However, CPT has poor pharmacokinetic properties, causes toxicities, and leads to drug resistance, which limit its clinical use. In this paper, review the current state of research. We first briefly explain CPT's TOP1 inhibition mechanism key hurdles in development. Then we examine strategies overcome limitations through structural modifications advanced delivery systems. Though alone seem insufficient fully enhance therapeutic potential, structure-activity relationship analysis provides insights guide optimization analogs. comparison, systems integrating controlled release, imaging capabilities, combination therapies via stimulus-responsive linkers moieties show great promise for improving pharmacological profile. Looking forward, multifaceted approaches combining selective derivatives with systems, informed by emerging biological insights, hold unleashing potential.

Язык: Английский

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Self‐Assembly of Rod‐Coil Bottlebrush Copolymers into Degradable Nanodiscs with a UV‐Triggered Self‐Immolation Process

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(13)

Опубликована: Фев. 7, 2024

Abstract Polymer nanodiscs, especially with stimuli‐responsive features, represent an unexplored frontier in the nanomaterial landscape. Such 2D nanomaterials are considered highly promising for advanced biomedicine applications. Herein, we designed a rod‐coil copolymer architecture based on amphiphilic, tadpole‐like bottlebrush copolymer, which can directly self‐assemble into core–shell nanodiscs aqueous environment. As side chains made of amorphous, UV‐responsive poly(ethyl glyoxylate) (PEtG) chains, they undergo rapid end‐to‐end self‐immolation upon light irradiation. This triggered nanodisc disassembly be used to boost small molecule release from core, is further aided by morphological change discs spheres.

Язык: Английский

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Precise Preparation of Size-Uniform Two-Dimensional Platelet Micelles Through Crystallization-Assisted Rapid Microphase Separation Using All-Bottlebrush-Type Block Copolymers with Crystalline Side Chains

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Янв. 3, 2025

Polymer nanoparticles with low curvature, especially two-dimensional (2D) soft materials, are rich in functions and outstanding properties have received extensive attention. Crystallization-driven self-assembly (CDSA) of linear semicrystalline block copolymers is currently a common method constructing 2D platelets uniform size. Although accompanied by high controllability, this CDSA usually inevitably requires longer aging time lower assembly concentration, limiting the large-scale preparation nanoaggregates. In study, series all-bottlebrush-type copolymers, poly(octadecyl acrylate)-block-poly(oligoethylene glycol methyl ether methacrylate)s prepared living polymerization. Driven synergistic crystallization crystalline side chains rapid microphase separation bottlebrush topology, these polymers can assemble into circular platelet micelles few minutes, without being affected concentration. process, epitaxial growth molecules proceeds rigid cylindrical molecular conformation at micelle sites eventually provides sandwich-type according to head-to-head stacking mode. This explained as "crystallization-assisted separation" mechanism. The structures solvent temperature, size which shows dependence on temperature below melting point block, be used precisely control morphology platelets. study establishes an efficient prepare polymer nanosoft promising candidates for further development, preparation, application various nanomaterials.

Язык: Английский

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Nanomaterials: leading immunogenic cell death-based cancer therapies

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Авг. 9, 2024

The field of oncology has transformed in recent years, with treatments shifting from traditional surgical resection and radiation therapy to more diverse customized approaches, one which is immunotherapy. ICD (immunogenic cell death) belongs a class regulatory death modalities that reactivate the immune response by facilitating interaction between apoptotic cells releasing specific signaling molecules, DAMPs (damage-associated molecular patterns). inducers can elevate expression proteins optimize TME (tumor microenvironment). use nanotechnology shown its unique potential. Nanomaterials, due their tunability, targeting, biocompatibility, have become powerful tools for drug delivery, immunomodulators, etc., significant efficacy clinical trials. In particular, these nanomaterials effectively activate ICD, trigger potent anti-tumor response, maintain long-term tumor suppression. Different types nanomaterials, such as biological membrane-modified nanoparticles, self-assembled nanostructures, metallic mesoporous materials, hydrogels, play respective roles induction structures mechanisms action. Therefore, this review will explore latest advances application common discuss how they provide new strategies cancer therapy. By gaining deeper understanding mechanism action researchers develop precise effective therapeutic approaches improve prognosis quality life patients. Moreover, hold promise overcome resistance conventional therapies, minimize side effects, lead personalized treatment regimens, ultimately benefiting treatment.

Язык: Английский

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Crystalline Nanoflowers Derived from the Intramolecular Cyclization-Induced Self-Assembly of an Amorphous Poly(amic acid) at High Solid Content

ACS Macro Letters, Год журнала: 2024, Номер 13(9), С. 1139 - 1146

Опубликована: Авг. 15, 2024

The investigation of the amorphous to crystalline transformation and corresponding influence on self-assembly behavior amphiphilic polymers are significant interest in this field. Herein, we propose concept intramolecular cyclization-induced (ICISA) prepare nanoflowers at a high solid content 15% basis poly(amic acid) (PAA). Taking advantage reactive property PAA, rigid polyimide (PI) segments introduced backbone PAA give P(AA-

Язык: Английский

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Regulating the Chirality of the Superhelices Self-Assembled from Block Copolymer/Homopolymer Binary Systems by the Mixing Ratio of the Polymers

Macromolecules, Год журнала: 2024, Номер 57(14), С. 6514 - 6521

Опубликована: Июль 11, 2024

Язык: Английский

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Control over Aspect Ratio and Polymer Spatial Distribution of 2D Platelets via Living Crystallization-Driven Self-Assembly

Macromolecules, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 29, 2024

Язык: Английский

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Precision synthesize of diblock copolymers via free radical photopolymerization

Chemical Communications, Год журнала: 2024, Номер 60(79), С. 11072 - 11075

Опубликована: Янв. 1, 2024

Diblock copolymers of phenyl methacrylate (PMA) and butyl (BMA) were synthesized using dual-wavelength photopolymerization with a bifunctional photoinitiator 2-(4-(2-hydroxy-2-methylpropanoyl)phenoxy)ethyl(

Язык: Английский

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Symmetric Diblock Copolymers Form Versatile and Switchable Ultrasmall Nanoparticles

ACS Nano, Год журнала: 2025, Номер unknown

Опубликована: Янв. 14, 2025

Block copolymers (BCPs) can form nanoparticles having different morphologies that be used as photonic nanocrystals and are a platform for drug delivery, sensors, catalysis. In particular, BCP disk-like shape have been recently discovered. Such nanodisks the next-generation antitumor delivery carriers; however, applicability of existing is limited due to their poor or unknown ability respond external stimuli. this work, we showed simplest symmetric diblock in equilibrium reversibly switched into multitude various potentially applicable nanophotonics, biomedicine, hierarchical self-assembly. These structures include patchy onion-like nanoparticles, striped ellipsoids, mixed morphology nanocolloids, spherical micelles. The transitions between aforementioned sharp, direct, achieved by tuning block–block polymer–solvent incompatibility. We demonstrated versatility nanoparticle upon reducing size approximately two lamellar periods BCP. Upon aggregation such small larger assembly formed. turn, these bigger particles could many other including chain-like supramolecular aggregate multilayered nanoparticle. obtained our results performing self-consistent field theory calculations according an algorithm designed produce morphology. This work demonstrates prepared from type BCPs extremely tunable; therefore, become producing stimuli-responsive nanoparticles.

Язык: Английский

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Surface-Emanated Vertical Organic Semiconducting Nanobrushes

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Фев. 17, 2025

Polymer self-assembly offers an important route to construct well-defined nanostructures. However, it remains challenging assemble polymers into vertically oriented Here, we use a seed-induced confinement strategy aligned semiconducting nanobrushes from polyfluorene-based on conductive substrates. Mechanism studies elucidate that the immobilized seeds substrate initiate vertical growth of nanobrushes, and supercritical drying as well rigid charged coronas collectively contribute retaining architecture. This process enables with ∼40× higher charge mobilities than their bulk film counterparts. Thus, inverted organic solar cells using electron transporting layer (ETL) exhibit record power conversion efficiency 18.51% result increased ETL texturing ETL-active interface favoring extraction. Moreover, our approach also uniform nanoporous photoanode (bismuth vanadate) for photoelectrochemical water splitting, improving catalyst distribution transfer. Our work presents feasible fabricating polymer nanostructures, thereby unlocking tremendous potential conjugated in optoelectronic applications.

Язык: Английский

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